Overexpression of ATPase Na+/+ transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma.
Overexpression of ATPase Na+/+ transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma.
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DOI：
10.18632/oncotarget.13267
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发表时间：
2016-12-20
期刊：
影响因子：
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通讯作者：
Wu MT
中科院分区：
文献类型：
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作者：
Wu IC;Chen YK;Wu CC;Cheng YJ;Chen WC;Ko HJ;Liu YP;Chai CY;Lin HS;Wu DC;Wu MT
本研究的目的是确定新的上调基因相关的分泌或膜蛋白，以帮助检测食管鳞状细胞癌（ESCC）。首先，我们进行了基于微阵列的筛选食管肿瘤从N-亚硝基甲基苄胺和阿托伐他汀诱导的F344大鼠和17人ESCC标本。候选基因通过定量PCR（qPCR）和ESCC组织的免疫组织化学（IHC）染色进行验证。在14例食管鳞癌患者的癌组织和癌旁正常组织中，10对（71.4%）通过qPCR检测到ATP酶Na +/K+转运α 1多肽（ATP酶Na +/K+转运α 1多肽）过表达（P = 0.0052）。应用组织芯片技术和ELISA法检测了243例食管鳞癌组织和126例癌旁正常组织中ATP 1A1蛋白的表达。ATP1A1在癌组织中过表达的可能性是正常组织的12.3倍（校正比值比= 12.3，95%CI = 7.2 - 21.0）。ATP1A1表达与肿瘤分期有关。血清ATP 1A1水平较高的患者发生晚期疾病（III-IV期vs. I-II期）的风险为2.9倍（95% CI = 1.1 - 7.4）。ATP1A1表达下调可抑制食管鳞癌细胞系的体外迁移和侵袭能力。我们的结论是ATP 1A1的过度表达与食管鳞癌的存在和严重程度密切相关。
This study aims to identify new upregulated genes related to secretory or membranous proteins to help detect esophageal squamous cell carcinoma (ESCC). First, we performed microarray-based screening of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and seventeen human ESCC specimens. Candidate genes were validated by quantitative PCR (qPCR) and immunohistochemical (IHC) staining of ESCC tissues. Among the paired cancer and adjacent normal tissues from 14 ESCC patients, 10 pairs (71.4%) had overexpression of ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) by qPCR (P = 0.0052). ATP1A1 protein expression was re-confirmed by tissue arrays in 243 ESCC tissues and 126 adjacent normal tissues and by ELISA in 78 serum specimens of ESCC patients. ATP1A1 was 12.3 times (adjusted odds ratio=12.3, 95% CI = 7.2-21.0) more likely to be overexpressed in cancer tissues than in normal tissues. ATP1A1 expression was also correlated to tumor stage. Patients with higher serum ATP1A1 levels had a 2.9-fold (95% CI = 1.1-7.4) risk of late-stage disease (stages III-IV vs. I-II). Downregulation of ATP1A1 expression inhibited the migration and invasion ability of ESCC cell lines in vitro. We concluded that the overexpression of ATP1A1 is strongly associated with the presence and severity of ESCC.